Hemoglobin A1c Has Suboptimal Performance to Diagnose and Monitor Diabetes Mellitus in Patients with Cirrhosis

Background: Glycated hemoglobin A1c (HbA1c) is routinely used to diagnose and monitor type 2 diabetes mellitus (T2DM) in cirrhotic patients. Remarkably, HbA1c may be falsely low in such patients. Aims: We assessed the diagnostic and monitoring yield of HbA1c in cirrhotic patients with T2DM (DM-Cirr) and without T2DM (NoDM-Cirr). Methods: We conducted a composite study allocating 21 NoDM-Cirr into a cross-sectional module and 16 DM-Cirr plus 13 controls with T2DM only (DM-NoCirr) into a prospective cohort. Oral glucose tolerance test (OGTT) was performed in NoDM-Cirr. DM-Cirr and DM-NoCirr were matched by sex, age, BMI, and T2DM treatment and studied with continuous glucose monitoring (CGM). Percent deviations from target, low/high blood glucose indexes (LBGI/HBGI) were calculated from CGM, as well as the average daily risk range (ADRR) as a marker of glucose variability. Results: Overall, HbA1c and OGTT diagnostic yield agreed in 12 patients (57%, ρ = 0.45, p < 0.03). CGM captured 3463 glucose determinations in DM-Cirr and 4273 in DM-NoCirr (p = 0.42). Regression analysis showed an inferior association between HbA1c and CGM in DM-Cirr (R ² = 0.52), when compared to DM-NoCirr (R ² = 0.94), and fructosamine did not improve association for DM-Cirr (R ² = 0.31). Interestingly, cirrhosis and Child–Turcotte–Pugh class accounted for HbA1c variance (p < 0.05). Patients in DM-Cirr were less frequently within target glucose (70–180 mg/dL), but at higher risk for hyperglycemia (HBGI > 9) when compared to DM-NoCirr, and they also showed higher glucose variability (ADRR 13.9 ± 2.5 vs. 8.9 ± 1.8, respectively, p = 0.03). Conclusion: HbA1c inaccurately represents chronic glycemia in patients with cirrhosis, likely in relation to increased glucose variability.